{"id":"https://openalex.org/W4392698673","doi":"https://doi.org/10.1158/1535-7163.c.6538957.v1","title":"Data from The Combination of Vemurafenib and Procaspase-3 Activation Is Synergistic in Mutant BRAF Melanomas","display_name":"Data from The Combination of Vemurafenib and Procaspase-3 Activation Is Synergistic in Mutant BRAF Melanomas","publication_year":2023,"publication_date":"2023-04-03","ids":{"openalex":"https://openalex.org/W4392698673","doi":"https://doi.org/10.1158/1535-7163.c.6538957.v1"},"language":"en","primary_location":{"id":"doi:10.1158/1535-7163.c.6538957.v1","doi":"https://doi.org/10.1158/1535-7163.c.6538957.v1","is_oa":true,"landing_page_url":"https://doi.org/10.1158/1535-7163.c.6538957.v1","pdf_url":null,"source":null,"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"American Association for Cancer Research","raw_type":"posted-content"},"volume":null,"type":"other","indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"gold","oa_url":"https://doi.org/10.1158/1535-7163.c.6538957.v1","any_repository_has_fulltext":null},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5038891328","display_name":"Jessie Peh","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Jessie Peh","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5012219010","display_name":"Timothy M. Fan","orcid":"https://orcid.org/0000-0003-2510-7050","observed_orcids":["https://orcid.org/0000-0003-2510-7050"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Timothy M. Fan","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5050890809","display_name":"Kathryn L. Wycislo","orcid":"https://orcid.org/0000-0002-3074-6044","observed_orcids":["https://orcid.org/0000-0002-3074-6044"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Kathryn L. Wycislo","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5113786729","display_name":"Howard S. Roth","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Howard S. Roth","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"last","author":{"id":"https://openalex.org/A5027996458","display_name":"Paul J. Hergenrother","orcid":"https://orcid.org/0000-0001-9018-3581","observed_orcids":["https://orcid.org/0000-0001-9018-3581"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Paul J. Hergenrother","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]}],"institutions":[],"countries_distinct_count":0,"institutions_distinct_count":0,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11533","display_name":"Melanoma and MAPK Pathways","score":1.0,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T11533","display_name":"Melanoma and MAPK Pathways","score":1.0,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10294","display_name":"Cell death mechanisms and regulation","score":0.0,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T12104","display_name":"Protein Tyrosine Phosphatases","score":0.0,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/vemurafenib","display_name":"vemurafenib","score":0.9990000128746033},{"id":"https://openalex.org/keywords/pac-1","display_name":"PAC-1","score":0.9330000281333923},{"id":"https://openalex.org/keywords/braf-v600e-mutation","display_name":"BRAF V600E mutation","score":0.8679999709129333},{"id":"https://openalex.org/keywords/melanoma","display_name":"melanoma","score":0.9049999713897705},{"id":"https://openalex.org/keywords/drug-synergy","display_name":"drug synergy","score":0.5830000042915344},{"id":"https://openalex.org/keywords/vemurafenib-resistance","display_name":"vemurafenib resistance","score":0.9399999976158142},{"id":"https://openalex.org/keywords/mapk-signaling-inhibition","display_name":"MAPK signaling inhibition","score":0.8289999961853027},{"id":"https://openalex.org/keywords/apoptosis","display_name":"apoptosis","score":0.6399999856948853},{"id":"https://openalex.org/keywords/caspase-3","display_name":"caspase-3","score":0.8730000257492065},{"id":"https://openalex.org/keywords/trametinib","display_name":"trametinib","score":0.9559999704360962},{"id":"https://openalex.org/keywords/mek-inhibitors","display_name":"MEK inhibitors","score":0.8650000095367432}],"concepts":[{"id":"https://openalex.org/C2776131300","wikidata":"https://www.wikidata.org/wiki/Q423111","display_name":"Vemurafenib","level":4,"score":0.9676545262336731},{"id":"https://openalex.org/C143065580","wikidata":"https://www.wikidata.org/wiki/Q3285695","display_name":"Mutant","level":3,"score":0.7254568338394165},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.6043113470077515},{"id":"https://openalex.org/C2777658100","wikidata":"https://www.wikidata.org/wiki/Q180614","display_name":"Melanoma","level":2,"score":0.5672856569290161},{"id":"https://openalex.org/C2776470698","wikidata":"https://www.wikidata.org/wiki/Q21851559","display_name":"V600E","level":4,"score":0.4356740713119507},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.33933955430984497},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.29326966404914856},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.29292112588882446},{"id":"https://openalex.org/C2994587330","wikidata":"https://www.wikidata.org/wiki/Q180614","display_name":"Metastatic melanoma","level":3,"score":0.26908808946609497},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.240128755569458},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.10828587412834167},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.07777976989746094}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1158/1535-7163.c.6538957.v1","doi":"https://doi.org/10.1158/1535-7163.c.6538957.v1","is_oa":true,"landing_page_url":"https://doi.org/10.1158/1535-7163.c.6538957.v1","pdf_url":null,"source":null,"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"American Association for Cancer Research","raw_type":"posted-content"}],"best_oa_location":{"id":"doi:10.1158/1535-7163.c.6538957.v1","doi":"https://doi.org/10.1158/1535-7163.c.6538957.v1","is_oa":true,"landing_page_url":"https://doi.org/10.1158/1535-7163.c.6538957.v1","pdf_url":null,"source":null,"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"American Association for Cancer Research","raw_type":"posted-content"},"sustainable_development_goals":[{"score":0.9537000060081482,"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W2428867055","https://openalex.org/W2053578467","https://openalex.org/W2505591268","https://openalex.org/W2171367970","https://openalex.org/W4323314184","https://openalex.org/W4244963342","https://openalex.org/W6962377331","https://openalex.org/W2087815516","https://openalex.org/W2885192271","https://openalex.org/W2102686544"],"abstract_inverted_index":{"Abstract":[0],"The":[1],"development":[2,194],"of":[3,10,15,23,39,53,100,107,122,127,135,172,189,195],"vemurafenib":[4,28,59,108,155,190],"resistance":[5],"limits":[6],"the":[7,19,51,76,81,103,116,123,133,186,193],"long-term":[8],"efficacy":[9],"this":[11],"drug":[12],"for":[13],"treatment":[14,138],"metastatic":[16],"melanomas":[17],"with":[18,27,139,154,176],"V600EBRAF":[20,77],"mutation.":[21,78],"Inhibition":[22],"downstream":[24],"MAPK":[25,173],"signaling":[26,174],"induces":[29],"apoptotic":[30,68],"cell":[31,69,73,150,162],"death":[32,70],"mediated":[33],"by":[34],"caspase-3,":[35],"suggesting":[36],"that":[37,50,98,170],"addition":[38,99,126],"a":[40,55,84,110],"procaspase-3":[41,178],"activator":[42],"could":[43],"enhance":[44,185],"anticancer":[45],"effects.":[46,94],"Here,":[47],"we":[48],"show":[49],"combination":[52,82,106],"PAC-1,":[54],"procaspase-activating":[56],"compound,":[57],"and":[58,67,90,109,119,152,191],"is":[60,180],"highly":[61],"synergistic":[62],"in":[63,71,88,149,164],"enhancing":[64],"caspase-3":[65,117],"activity":[66,118,188],"melanoma":[72],"lines":[74],"harboring":[75],"In":[79],"vivo,":[80],"displays":[83],"favorable":[85],"safety":[86],"profile":[87],"mice":[89],"exerts":[91],"significant":[92],"antitumor":[93,158,187],"We":[95],"further":[96],"demonstrate":[97],"PAC-1":[101,130,142],"to":[102,156,184],"clinically":[104],"useful":[105],"MEK":[111],"inhibitor,":[112],"trametinib,":[113],"starkly":[114],"enhances":[115],"proapoptotic":[120],"effect":[121],"combination.":[124],"Moreover,":[125],"low":[128],"concentration":[129],"also":[131],"delays":[132],"regrowth":[134],"cells":[136,148],"following":[137],"vemurafenib.":[140],"Finally,":[141],"remains":[143],"potent":[144],"against":[145],"vemurafenib-resistant":[146],"A375VR":[147,161],"culture":[151],"synergizes":[153],"exert":[157],"effects":[159],"on":[160],"growth":[163],"vivo.":[165],"Collectively,":[166],"our":[167],"data":[168],"suggest":[169],"inhibition":[171],"combined":[175],"concurrent":[177],"activation":[179],"an":[181],"effective":[182],"strategy":[183],"mitigate":[192],"resistance.":[196],"Mol":[197],"Cancer":[198],"Ther;":[199],"15(8);":[200],"1859\u201369.":[201],"\u00a92016":[202],"AACR.":[203]},"counts_by_year":[],"updated_date":"2026-08-21T09:56:20.448147","created_date":"2024-03-13T00:00:00"}
